Evidence of impaired macroautophagy in human degenerative cervical myelopathy

• Published in: Scientific reports Vol. 12; no. 1; p. 11873
• Main Authors: Smith, Sam S., Young, Adam M. H., Davies, Benjamin M., Takahashi, Hitoshi, Allinson, Kieren S. J., Kotter, Mark R. N.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13-07-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 631/80/39; 692/617/375/1824; Autophagy; Bcl-2 protein; Central nervous system diseases; Cervical Vertebrae; Humanities and Social Sciences; Humans; Macroautophagy; multidisciplinary; Neurodegenerative diseases; Pathophysiology; Proto-Oncogene Proteins c-bcl-2; Science; Science (multidisciplinary); Spinal cord; Spinal Cord Diseases; Tau protein; Therapeutic targets
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-15158-x

Degenerative cervical myelopathy (DCM) is a common progressive disease of the spinal cord which can cause tetraplegia. Despite its prevalence, few studies have investigated the pathophysiology of DCM. Macroautophagy is a cellular process which degrades intracellular contents and its disruption is thought to contribute to many neurodegenerative diseases. The present study tests the hypothesis that macroautophagy is impaired in DCM. To address this, we utilised a collection of post-mortem cervical spinal cord samples and investigated seven DCM cases and five human controls. Immunohistochemical staining was used to visualise proteins involved in autophagy. This demonstrated significantly reduced numbers of LC3 puncta in cases versus controls (p = 0.0424). Consistent with reduced autophagy, we identified large aggregates of p62 in four of seven cases and no controls. Tau was increased in two of five cases compared to controls. BCL-2 was significantly increased in cases versus controls (p = 0.0133) and may explain this reduction in autophagy. Increased BCL-2 (p = 0.0369) and p62 bodies (p = 0.055) were seen in more severe cases of DCM. This is the first evidence that autophagy is impaired in DCM; the impairment appears greater in more severe cases. Further research is necessary to investigate whether macroautophagy has potential as a therapeutic target in DCM.